FDA Grants Priority Review for Next-Gen BCL2 Inhibitor Sonrotoclax in MCL

Sonrotoclax (BGB-11417), an investigational, next-generation BCL2 inhibitor, has received priority review designation from the FDA for the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) following prior therapy with a Bruton tyrosine kinase (BTK) inhibitor.¹

The FDA acceptance of the new drug application (NDA) for sonrotoclax marks a significant regulatory acceleration, indicating the potential for this agent to offer a substantial improvement in the safety or effectiveness of treatment for this serious, high-unmet-need condition. With this priority review, the FDA aims to make a decision within 6 months compared with the standard 10 months.

The priority review status, coupled with a prior breakthrough therapy designation, underscores the promising efficacy and manageable safety profile demonstrated in the supporting phase 1/2 BGB-11417-201 study (NCT05471843).

“Sonrotoclax is advancing with remarkable speed, from breakthrough therapy designation to priority review, all within a short window,” said Lai Wang, PhD, global head of Research and Development at BeOne Medicines, in a news release. “That pace reflects both the strength of the data and the urgency of the need for patients with R/R MCL.”

MCL, an aggressive and typically late-stage non-Hodgkin lymphoma (NHL) accounting for approximately 5% of all NHL cases, presents a critical challenge in the R/R setting, especially after BTK inhibitor failure. With a 5-year survival rate of approximately 50%, the need for novel, effective, and tolerable therapeutic options is urgent.

Clinical Foundation: BGB-11417-201 Study Met Primary End Point

The NDA submission is primarily supported by data from the global, multicenter phase 1/2 study, BGB-11417-201, which evaluated the efficacy and safety of sonrotoclax monotherapy in a heavily pretreated R/R MCL cohort of 125 adult patients.

The study successfully achieved its primary end point of overall response rate as determined by an independent review committee, with responses described as clinically meaningful in this challenging, post-BTK inhibitor population. Key secondary end points also demonstrated encouraging results, including the complete response rate, duration of response, and progression-free survival.² Furthermore, sonrotoclax was reported to exhibit a well-tolerated safety profile, with manageable risks consistent with its mechanism of action as a BCL2 inhibitor. Full clinical results from the BGB-11417-201 study are scheduled for oral presentation at the upcoming 67th American Society of Hematology (ASH) Annual Meeting and Exposition.¹

Mechanism and Clinical Program Profile

Sonrotoclax is classified as a next-generation inhibitor of the BCL2 protein. BCL2 is an antiapoptotic protein that is highly expressed in many B-cell malignancies, including MCL, promoting cell survival and conferring resistance to chemotherapy. By selectively inhibiting BCL2, sonrotoclax aims to restore the apoptotic pathway in malignant B-cells, leading to programmed cell death.

In early development studies, the compound demonstrated properties consistent with a potentially "best-in-class" profile, including high potency, a short half-life, and an absence of drug accumulation, potentially offering pharmacokinetic advantages and improved manageability of on-target adverse effects.

Beyond R/R MCL, the global development program for sonrotoclax is extensive, having enrolled over 2200 patients across various hematologic malignancies, exploring its utility as both a monotherapy and in combination regimens. Notably, early clinical trials investigating the combination of sonrotoclax with the BTK inhibitor, zanubrutinib (Brukinsa), in treatment-naive chronic lymphocytic leukemia (CLL) demonstrated rapid and substantial rates of undetectable minimal residual disease, highlighting its potential as a backbone agent in novel combination strategies.

REFERENCES

1. U.S. FDA grants priority review to sonrotoclax for the treatment of relapsed or refractory mantle cell lymphoma. News release. BeOne Medicines. November 26, 2025. Accessed November 26, 2025. https://tinyurl.com/vwfhr8sc

2. Study of BGB-11417 monotherapy in participants with relapsed or refractory mantle cell lymphoma. ClinicalTrials.gov. Updated September 9, 2025. Accessed November 26, 2025. https://clinicaltrials.gov/study/NCT05471843